Researchers at the University of Illinois Urbana-Champaign have developed SPLICER, a novel gene editing tool that effectively skips disease-causing gene segments. In a study published in Nature Communications, Professor Pablo Perez-Pinera and his team demonstrated SPLICER’s ability to reduce amyloid-beta plaque precursors in a mouse model of Alzheimer’s disease.
How SPLICER Works: SPLICER employs an exon skipping technique to bypass faulty gene sections that produce harmful proteins. Unlike traditional CRISPR-Cas9 systems, SPLICER uses advanced Cas9 enzymes that do not require specific DNA sequences, allowing it to target a wider range of genes. This makes SPLICER versatile for treating various genetic disorders, including Duchenne’s muscular dystrophy and Huntington’s disease.
Key Achievements:
- Enhanced Efficiency: In live mice, SPLICER successfully reduced the targeted exon by 25%, lowering amyloid-beta formation without off-target effects.
- Precision Improvement: By editing both the start and end sequences around an exon, SPLICER ensures more accurate skipping, preventing incomplete gene edits.
- Broad Potential: The tool’s effectiveness in Alzheimer’s models suggests it could be adapted for other diseases caused by toxic or misfolded proteins.
Expert Insights: Graduate student Angelo Miskalis highlighted, “SPLICER improves exon skipping precision, ensuring the entire problematic exon is bypassed.” Shraddha Shirguppe added, “SPLICER outperforms older methods, effectively reducing plaque-producing proteins.”
Future Directions: While exon skipping shows great promise, it is only viable if the resulting protein remains functional. The next steps include verifying the safety of removing targeted exons, ensuring no new toxic proteins are formed, and conducting long-term animal studies to monitor disease progression.
Support and Collaboration: The research, supported by the NIH, Muscular Dystrophy Association, and other foundations, involved collaborations with Sergei Maslov and Thomas Gaj. Professor Neumann’s team continues to explore SPLICER’s applications, aiming to advance personalized medicine and therapeutic interventions for complex genetic diseases.